Signs of Autism Show Up on MRI at 6 Months of Age

Children who develop autism have pervasive abnormalities of brain white matter and altered neural developmental trajectories even before symptoms appear, researchers demonstrated on imaging studies.

At 6 months of age, at-risk infants who later showed typical symptoms of autism had higher fractional anisotropy on MRI, reflecting increased anxonal diameter, myelination, and fiber density in areas such as the left fornix (P=0.04) and the left inferior longitudinal fasciculus (P=0.01), according to Jason J. Wolff, PhD, of the University of North Carolina in Chapel Hill, and colleagues.

But by 24 months, at-risk children who did not develop the disorder had higher anisotropic values in the left anterior limb of the internal capsule (P=0.04) and for left anterior thalamic radiation (P=0.003), the researchers reported online in the American Journal of Psychiatry.

Action Points

Note that children who develop autism have pervasive abnormalities of brain white matter and altered neural developmental trajectories even before symptoms appear.

Note that by 24 months, at-risk children who did not develop the disorder had higher anisotropic values in the left anterior limb of the internal capsule and for left anterior thalamic radiation.

"Autism is increasingly considered a disorder characterized in part by aberrant neural circuitry," they wrote.

An enlarging body of literature is demonstrating that the abnormalities involve several areas of white matter, but the extent and course of these developmental anomalies -- beginning as early as 6 months -- have not previously been explored.

Accordingly, Wolff and colleagues enrolled 92 children considered to be at risk for autism because they had a sibling with the disorder, and performed diffusion tensor imaging beginning at 6 months of age.

The MRI scans -- done while the children slept -- were repeated at 12 months and 24 months, along with cognitive testing on the Mullen Scales of Early Learning.

At age 2, the children were assessed for behavioral development using the Autism Diagnostic Observation Schedule; at that time 28 infants met the criteria for autism spectrum disorder.

The affected infants also had scores on the Mullen scales that were 12 points lower than the children who developed normally (P=0.04).

The researchers scanned a total of 15 white matter tracts in each child and identified significant differences in trajectories for 12 of the tracts, with rapid changes occurring in the normal infants between 6 and 24 months.

"Most fiber tracts for the [autism spectrum disorder]-positive infants were characterized by higher fractional anisotropy at 6 months followed by blunted developmental trajectories such that fractional anisotropy was lower by 24 months," observed Wolff and colleagues.

The widespread nature of the abnormalities suggests that multiple areas of the brain are affected in autism, and the fact that changes were detected in advance of symptoms argues in favor of a "neurobiological foundation" for autism.

Both structural and experiential processes contribute to the development of the brain, and the physical abnormalities seen on MRI in this study may interfere with fine neural signal transmission capabilities needed for successful social learning, resulting in the behavioral disturbances that begin to be seen around 2 years of age, the researchers explained.

They recommended further work to extend brain imaging even earlier than 6 months in at-risk children in the hope of identifying markers that signal incipient developmental dysregulation.

"Identifying infants at highest risk for [autism spectrum disorders] before the full syndrome is manifest offers the possibility of implementing interventions that could reduce or even prevent the manifestation of the full syndrome," they wrote.

Limitations of the study included the lack of a low-risk control group, and reliance on fractional anisotropy to assess white matter development.

The study was supported by the National Institute of Child Health and Development, Autism Speaks, the Simons Foundation, and the National Alliance for Medical Image Computing.

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